tbuckley/cabot-search huggingface dataset:
Systemic Therapy for Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: ASCO Guideline Update
Authors: Sharon H. Giordano, Maria Alice B. Franzoi, Sarah Temin, Carey K. Anders, Sarat Chandarlapaty, Jennie R. Crews, Jeffrey J. Kirshner, Ian E. Krop, Nancy U. Lin, Aki Morikawa, Debra A. Patt, Jane Perlmutter, Naren Ramakrishna, Nancy E. Davidson
Journal: Journal of Clinical Oncology (2022)

To update evidence-based guideline recommendations to practicing oncologists and others on systemic therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer.An Expert Panel conducted a targeted systematic literature review (for both systemic treatment and CNS metastases) and identified 545 articles. Outcomes of interest included efficacy and safety.Of the 545 publications identified and reviewed, 14 were identified to form the evidentiary basis for the guideline recommendations.HER2-targeted therapy is recommended for patients with HER2-positive advanced breast cancer, except for those with clinical congestive heart failure or significantly compromised left ventricular ejection fraction, who should be evaluated on a case-by-case basis. Trastuzumab, pertuzumab, and taxane for first-line treatment and trastuzumab deruxtecan for second-line treatment are recommended. In the third-line setting, clinicians should offer other HER2-targeted therapy combinations. There is a lack of head-to-head trials; therefore, there is insufficient evidence to recommend one regimen over another. The patient and the clinician should discuss differences in treatment schedule, route, toxicities, etc during the decision-making process. Options include regimens with tucatinib, trastuzumab emtansine, trastuzumab deruxtecan (if either not previously administered), neratinib, lapatinib, chemotherapy, margetuximab, hormonal therapy, and abemaciclib plus trastuzumab plus fulvestrant, and may offer pertuzumab if the patient has not previously received it. Optimal duration of chemotherapy is at least 4-6 months or until maximum response, depending on toxicity and in the absence of progression. HER2-targeted therapy can continue until time of progression or unacceptable toxicities. For patients with HER2-positive and estrogen receptor-positive or progesterone receptor-positive breast cancer, clinicians may recommend either standard first-line therapy or, for selected patients, endocrine therapy plus HER2-targeted therapy or endocrine therapy alone.Additional information is available at www.asco.org/breast-cancer-guidelines.
Granulomatous slack skin: clinical characteristics, prognosis and response to therapy. A study from the Cutaneous Lymphoma French Study Group
Authors: Gilles Battesti, Caroline Ram-Wolff, Gabor Dobos, François Aubin, Marie-Paule Algros, Emmanuella Guenova, Pascal Joly, Philippe Courville, Samia Mourah, Jean-Michel Cayuela, Jean-David Bouaziz, Hélène Moins-Teisserenc, Maxime Battistella, Marie-Dominique Vignon-Pennamen, Jacqueline Rivet, Martine Bagot, Adèle de Masson
Journal: British Journal of Dermatology (2022)

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LGG-64. A Phase II Study of Pegylated Interferon in Children with Recurrent or Refractory and Radiographically or Clinically Progressive Juvenile Pilocytic Astrocytomas and Optic Pathway Gliomas (NCT02343224)
Authors: Dolly Aguilera, Claire Mazewski, Anna Janss, Tobey MacDonald, Adam Goldman, Tracy Leong, Robert Craig Castellino
Journal: Neuro-Oncology (2022)

Abstract Unresectable Juvenile Pilocytic Astrocytomas (JPA) and Optic Pathway gliomas (OPG) are chronic diseases that can have solid +/- cystic components. We wanted to evaluate the objective response to pegylated interferon Alpha2B in this group of patients in a prospective single arm Phase II clinical trial. Eligibility criteria: age 3 -25 years, patients with neurofibromatosis (NF) were eligible, evidence of measurable disease in MRI, no limitation in the number of prior therapies including chemotherapy and radiation. Exclusion criteria: prior pegylated interferon exposure, less than 2 years from radiation, active autoimmune disease. Subjects enrolled received pegylated interferon 1 mcg/kg/dose SQ weekly, to a max dose of 150mcg/dose in 28 day cycles for up to 2 years. The study design is a Simon two stage design. If no complete or partial responses among the first 9 patients, the study will terminate. Nine subjects enrolled: 4 females, 5 males, median age of 11years, 6 Caucasians, 3 African Americans. Two subjects with NF. Molecular findings KIAA-BRAF fusion (6), V600E mutation (1), CDK2A loss (1). Location: brain (7), brain and spine (2). We enrolled a heavily pre-treated population, patients with prior radiation ( 1), nine with prior chemotherapy, the average number of regimens 4 (range 2-6). No complete responses or partial responses were seen. Two patients with prolonged stable disease 75+months and 66+ months. At 12 and 24 month EFS 76.2% (95%CI52.1-100%). Median EFS has not been reached. The 12 and 24 months survival estimate 75% (95% CI 50.3-100%), median survival has not been reached. Side effects as expected mostly grade 1-2. No grade 4 event related to pegylated interferon were seen. This is the first report of pegylated interferon in OPG and JPA, two patients with prolonged stable disease suggesting that pegylated interferon can offer potential benefit in this population and additional studies are important.
Informatics tools to implement late cardiovascular risk prediction modeling for population health management of high-risk childhood cancer survivors.
Authors: David H Noyd, Amanda Janitz, Ashley Baker, William Beasley, Nancy Etzold, David Kendrick, Kevin C. Oeffinger
Journal: Journal of Clinical Oncology (2022)

10048 Background: Marked improvements in outcomes for children with cancer and robust cohort studies with longitudinal follow-up inform evidence-based guidelines for survivors at risk for late cardiomyopathy. Clinical informatics tools to integrate data from multiple sources have the potential to catalyze population health management. Methods: The Oklahoma Childhood Cancer Survivor cohort was constructed from an institutional cancer registry of survivors diagnosed between 2005 and 2014 (n=382). Data elements (cumulative anthracycline, cumulative chest-directed radiotherapy, alkylator, and platinum exposures) were extracted from Passport for Care (PFC) to implement previously validated late cardiovascular risk prediction modeling from the Childhood Cancer Survivor Study (CCSS) for cardiomyopathy. Risk groups were compared to the Children’s Oncology Group (COG) Long-Term Follow-up Guidelines. Standard query language facilitated extraction of echocardiogram data from the electronic health record to determine adherence, defined as an echocardiogram within 27 months and 63 months from the last day of therapy for high and moderate risk survivors, respectively. Results: Sixty-nine percent (n=264) of survivors from the cancer registry were documented in PFC, of whom 29%, 56%, and 15% were classified as low, moderate, high risk, respectively, based on the CCSS late cardiomyopathy risk calculator. Concordance was modest for high and moderate risk groups (Kappa = 0.42 and 0.46, respectively) and good for the low risk group (Kappa = 0.77) compared to COG risk groups. There was excellent adherence to echocardiogram guidelines with 93% and 81% of moderate and high-risk survivors, respectively. There were significant differences based on risk group (p=0.02) and age at diagnosis (p&lt;0.01). Conclusions: Clinical informatics tools represent a feasible approach to leverage discrete data elements regarding key treatment exposures from PFC to successfully implement previously validated late cardiovascular risk prediction models on a population health level. PFC promotes adherence to echocardiogram surveillance and serves as a platform for future interoperability to generate real-world data to improve survivorship-focused care. [Table: see text]
Efficacy and safety of outpatient based therapy in childhood acute lymphoblastic leukemia.
Authors: Osman Bulent Zulfikar, Basak Koc
Journal: Journal of Clinical Oncology (2022)

e22001 Background: Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood. With the improvements in effective antileukemic drugs and the risk stratification treatment approach, the cure rate for pediatric ALL has increased to &gt;90%. The effect of outpatient treatment and developing supportive care have a very important role in this success. We evaluated the disease outcomes and severe complications (complication causes hospitalization in ICU, encephalitis) of children who had been treated with the Children’s Oncology Group (COG) protocols, and follow-up protocol during a 20-year study period. Methods: From 1999 to 2020, 134 patients who had been diagnosed with ALL in the Department of Pediatric Hematology-Oncology at the Istanbul University Oncology Institute were included in the present study. Nine patients excluded from all analysis that 5 of them admitted with relapse, 2 had been diagnosed with mature aggressive B-cell acute leukemia, and 2 had been diagnosed with mixed phenotype and 7 who had been lost to follow-up were also excluded from survival analyses. Results: Mean age was 7.7±4.89 years old in 125 patients (Table). The 5- and 10-year and 20-year Event Free Survival (EFS) rates were 90.2% (standard error [SE], 4.2%) in standart risk B-ALL (n=54) and Overall Survival (OS) rates were 100%, 96% and 96% ([SE], 3.9%), respectively. In high risk group B-ALL (n=53) 5-year EFS was 80.7% (standard error [SE], 5.8%) and 78.2% ([SE], 6.1%) for both 10 and 20 year period and OS rates were 76.9% ([SE], 5.9%) for all periods. Although the number of patients is low in T-ALL (n=11), 5- and 10-year and 20-year EFS and OS rates were 63.6% (standard error [SE], 14.5%) for all periods. Fifteen severe complication recorded in 12 patients (10 B-ALL, 2 T-ALL). One patient hospitalized in ICU due to gram negative sepsis for 3-times and epidural hemorrhage. Conclusions: The survival rate for pediatric ALL has increased in recent years according to improvements of treatment.In our cohort, 20-year OS rate is 96% for standart risk B-ALL and 76.9% for high risk B-ALL. Additionally, regularly and closely monitored patients, complications can be effectively prevented, treated, and eliminated. In our study, the short hospitalization period, rapid analysis of laboratory tests, continuous supportive care, efficient education given to the parents of children increased the success of the therapy and ensured low complication rates. [Table: see text]
Physician perspectives on extrapolating data from trials testing less-intense treatment to underrepresented populations.
Authors: Gabrielle Betty Rocque, Courtney J. Andrews, Valerie Lawhon, Stacey A. Ingram, Rachel Marie Frazier, Mary Lou Smith, Lynne I. Wagner, Lisa Zubkoff, Lauren P. Wallner, Antonio C. Wolff
Journal: Journal of Clinical Oncology (2022)

521 Background: Clinical trials provide the foundation for evidence-based practices, yet trial participants are often not representative of all patients. Historically, clinical trials involved adding novel agents to standard of care to improve survival. There has been a shift to an individualized approach with testing less intense treatment, yet vulnerable patient groups are at risk for underrepresentation. Little is known about physician perspectives on implementing less intense treatment approaches for patients who are not represented in sufficient number to draw conclusions on subpopulations. Methods: Open-ended, individual qualitative interviews with medical oncologists from different cancer centers exploring their perspectives on trials that test less intense treatment for patients with cancer. Interviews were audio-recorded and transcribed. Four independent coders utilized a content analysis approach to analyze transcripts using NVivo. Major themes and exemplary quotes were extracted. Results: Of the 39 participating physicians, 61.5% felt comfortable extrapolating, 30.8% were hesitant, and 7.7% would not feel comfortable extrapolating trial outcomes to underrepresented populations. One physician noted, “We've been extrapolating for as long as I can remember and certainly that I've been in practice; so we do need to do better there, but extrapolation is only natural with what we have.” Facilitators of comfort included sentiment that “biology is biology”, such that the cancer characteristics were what mattered; the strength of the evidence from the trial overall; inclusion of subset analysis on underrepresented populations; and prior experience making decisions with limited data. Barriers to extrapolation included the potential harm over the patient’s lifetime; concerns about groups that had minimal participants; application specifically to younger patients; and extending findings to racially and ethnically diverse populations. Oncologists highlighted the need for shared decision-making when applying study results to underrepresented populations. They also expressed concerns about study findings being applied to patients who would have been ineligible in the original trials. Universally, broader inclusion in trials testing lowering chemotherapy is desired. Conclusions: The majority (92%) of physicians report that they would extrapolate clinical trial results to patients poorly represented in de-escalation trials, while expressing concerns about applicability to specific subpopulations based on tumor characteristics (e.g. stage, biology) and patient demographics (e.g. age, race). Further work is needed to increase clinical trial representation of diverse populations to safely and effectively optimize treatment for patients with cancer.
Fear of negative evaluation in patients with hidradenitis suppurativa is correlated with worse quality of life: an observational study
Authors: Rohan Singh, Esther A. Balogh, Aditi Senthilnathan, Irma M. Richardson, Sebastian G. Kaplan, Steven R. Feldman, Rita O. Pichardo
Journal: British Journal of Dermatology (2022)

Journal Article Fear of negative evaluation in patients with hidradenitis suppurativa is correlated with worse quality of life: an observational study Get access Rohan Singh, Rohan Singh Center for Dermatology Research, Department of Dermatology https://orcid.org/0000-0001-6532-1639 Search for other works by this author on: Oxford Academic Google Scholar Esther A. Balogh, Esther A. Balogh Center for Dermatology Research, Department of Dermatology Search for other works by this author on: Oxford Academic Google Scholar Aditi Senthilnathan, Aditi Senthilnathan Center for Dermatology Research, Department of Dermatology Search for other works by this author on: Oxford Academic Google Scholar Irma M. Richardson, Irma M. Richardson Center for Dermatology Research, Department of Dermatology Search for other works by this author on: Oxford Academic Google Scholar Sebastian G. Kaplan, Sebastian G. Kaplan Department of Psychiatry and Behavioral Medicine Search for other works by this author on: Oxford Academic Google Scholar Steven R. Feldman, Steven R. Feldman Center for Dermatology Research, Department of DermatologyDepartment of PathologyDepartment of Public Health Sciences Wake Forest School of Medicine Winston‐Salem NC USA https://orcid.org/0000-0002-0090-6289 Search for other works by this author on: Oxford Academic Google Scholar Rita O. Pichardo Rita O. Pichardo Center for Dermatology Research, Department of Dermatology Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 187, Issue 5, 1 November 2022, Pages 788–790, https://doi.org/10.1111/bjd.21694 Published: 01 November 2022
A novel NGS kit solution for multi-cancer early detection using circulating cell free DNA based methylation analysis.
Authors: Grace Q. Zhao, Yun Bao, Heng Wang, Peter Vu, Sandip Pravin Patel, Shengrong Lin
Journal: Journal of Clinical Oncology (2022)

10542 Background: Cancer patient survival can be greatly improved by early detection. Cell-free DNA (cfDNA)-based cancer detection using targeted methylation sequencing (TMS) holds great promise. Here, we report the performance of the first cfDNA TMS kit for early cancer detection. Methods: We developed a comprehensive multi-cancer TMS panel, named “Omni1” (900kb) containing ̃3000 cancer specific hypermethylation markers for the detection of the 16 most prevalent solid tumor cancer types in the US. These selected biomarkers all have high signals in cancer, low signals in normal tissue and close to zero background in plasma. The TMS analysis is empowered by Point-n-Seq DNA enrichment and soft bisulfite sequencing technology. Across the different cancer types, the Point-n-Seq Methylation Index (PMI) derived from the Omni1 panel showed over 10 times the difference in the genomic DNA of tumor compared to normal tissues. 8 to 32 early-stage plasma samples from each of the 7 most prevalent cancer types were used for assay testing. cfDNA extracted from each donor was subjected to our Point-n-Seq TMS analysis with the Omni1 panel. The TMS workflow took around five hours, from cfDNA to a sequencing ready library. 6M reads were assigned to each sample resulting in ̃1400X average raw coverage across the target regions. Results: A computational model to calculate the methylation index and the thresholds were established on independent training data sets for each cancer type. For the testing, specificity was set at 89% (CI = 0.81, 0.97, n = 55 self-claimed healthy individuals). The detection rate for stage I (n = 55) and stage II (n = 56) of all 7 cancer types combined is 65% (CI = 0.53,0.78) and 75% (CI = 0.64, 0.86) respectively. Even within this small sample size, it was clear that the detection sensitivity varied among different cancer types, and it increased from stage I to II: colorectal (65%, n = 20; 75%, n = 12), lung (75% n = 8; 92%, n = 12), pancreas (80%, n = 10; 100%, n = 10), ovary (60%, n = 5; 80%, n = 5), breast (40%, n = 7; 100%, n = 3), and prostate cancer (0%, n = 2; 22% n = 9) for stage I and II respectively. A decrease in sensitivity from stage I to II in liver (100%, n = 3; 60%, n = 5) is possibly due to variability from the small sample size. For the cases of CRC, the detection rates obtained from Omni1 are comparable to the stand-alone CRC560 panel (170 kb). Conclusions: In this study we demonstrated that by leveraging an economy-size panel, a robust methylation sequencing kit, and a straightforward analysis methodology, early cancer detection for multiple cancer types can be done with just 1ml plasma. The kit strategy provides an easy-to-use and distributable solution, without the complications of developing a lab-specific test that uses a large methylation panel and a high sequencing cost.
Survival trends of patients with Paget disease of the breast: A National Cancer Database (NCDB) study.
Authors: Gia Thinh Truong, Zachary Creech, Regan Denny, Robert W. Hu, Kiana Verplancke, Peter T. Silberstein, Connor Tupper
Journal: Journal of Clinical Oncology (2022)

e12585 Background: Paget disease of the breast is a malignant tumor that comprises only 1-3% of all breast carcinomas. It may coexist with an underlying ductal carcinoma in situ or present alone without additional carcinomas. Due to the rarity of this carcinoma and minimal literature available, we intend to identify potentially important prognostic factors, particularly those of socioeconomic origin. Methods: We performed a retrospective investigation of 5,918 patients diagnosed with Paget Disease of the breast from the NCDB between 2004-2018. Patient demographic and clinical characteristics such as household income, insurance status, treatment center type, and treatment center location were extracted from the database. Survival rates were compared using Kaplan-Meier curves, log-rank test, univariate and chi-square analysis. Data were analyzed using SPSS statistics 27. Results: African American patients had higher mortality rates than Caucasian patients (p &lt; 0.005). Patients with underlying intraductal carcinoma of the breast had the highest survival rates (p &lt; 0.001). Patients who received immunotherapy as part of the treatment plan had a significantly higher survival rate than those who did not (136.97 vs. 144.24 months respectively, p &lt; 0.001). Patients coming from lower median household incomes had significantly lower survival rates. Specifically, patients with a household income of less than $38,000 had a lower mean survival rate compared to those with a household income of greater than $63,000 (122.74 months compared to 140.63, respectively, p &lt; 0.001). Those with private insurance had a higher mean survival time than those with Medicaid and no insurance (170.60, 138.13, and 130.69 months respectively, p &lt; 0.001). Patients from counties in metro areas with populations of 1 million or more had a significantly higher survival rate than those from counties in metro areas with less than 1 million (p &lt; 0.003). In addition, patients treated at academic centers had a higher mean survival rate than those treated at non-academic centers (p &lt; 0.001). Conclusions: Our results show significant variation in survival rates among patients based on their socioeconomic and treatment center characteristics. Additional research targeting patients with these characteristics can lead to improved clinical outcomes.
MEDB-34. A very rare case: medulloblastoma relapse with bone marrow infiltration in a toddler
Authors: Claudia Zinke, Gudrun Fleischhack, Julia Hauer, Björn Sönke Lange, Jenny Dörnemann, Gabriele Hahn, Gabriele Schackert, Kristin Gurtner, Matthias Meinhardt, Korinna Jöhrens, Ralf Knöfler
Journal: Neuro-Oncology (2022)

Abstract We report about a female toddler congenitally deaf and diagnosed with a non-metastatic desmoplastic medulloblastoma (SHH activated, TP53-wt, variant in LDB1 gene). No tumor predisposition syndrome was found. After complete tumor resection the patient was treated according to I-HIT-MED-Guidance protocol. Five months later an asymptomatic localised relapse (same histology, PTEN frameshift deletion, TERT mutation, LDB1 mutation) detected by routine MRI was treated by complete resection, craniospinal irradiation and an antiangiogenic regimen adapted from the MEMMAT scheme including fenofibrate, thalidomide, celecoxib, topotecan, temozolomide, bevacizumab and intraventricular cytarabine. Before start of systemic treatment blood cell counts were normal. In the second cycle we had to interrupt chemotherapy due to a leukopenia while continuing the antiangiogenic treatment. In order to avoid relevant bone marrow toxicity chemotherapy doses were reduced. Nevertheless we had to stop the fourth cycle because of a severe pancytopenia. Same time the girl presented with fever, neck and leg pain. A full blood count showed: hemoglobin 6.92 g/dl, leukocytes 640/µl, platelets 8,000/µl. Suspecting an infection supported by the presence of a high CrP value of 230 mg/l the patient was treated with i.v. antibiotics. MRI showed an unspecific retropharyngeal soft tissue augmentation, a pleural effusion and high T2 signals in multiple vertebral bodies but no central tumor relapse. The bone marrow diagnostics revealed a diffuse medulloblastoma cell infiltration with the known PTEN frameshift deletion and LDB1 mutation. The liquor was tumor-cell free. We report on an extremely rare case of an early local relapse of desmoplastic medulloblastoma progressing to a diffuse bone marrow infiltration in a toddler. The girl died due to therapy resistance 9 weeks after bone marrow relapse. It remains unclear whether the fatal course was related to the hereditary deafness syndrome and the molecular alterations of the tumor.
Type 2 cytokines in the thymus activate Sirpα+ dendritic cells to promote clonal deletion
Authors: Elise R. Breed, Matouš Vobořil, Katherine M. Ashby, Ryan J. Martinez, Lily Qian, Haiguang Wang, Oscar C. Salgado, Christine H. O’Connor, Kristin A. Hogquist
Journal: Nature Immunology (2022)